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Typus
KomplettPlagiat
Bearbeiter
Hindemith, Graf Isolan
Gesichtet
Yes.png
Untersuchte Arbeit:
Seite: 19, Zeilen: 1-12, 22-26
Quelle: Rajamanickam 2007
Seite(n): 11, 12, Zeilen: 11: 5ff; 12: 10ff
[SGK1 was found to stimulate Na+, K+ and 2Cl- cotransporter activity in the thick ascending limb of the] kidney, a key nephron segment in urinary concentration, which is of importance in renal Na+ reabsorption (85). Abundant SGK1 gene transcription has been observed in diabetic nephropathy (85-87), fibrosing pancreatitis (90) and inflammatory bowel disease (96) but SGK1 involvement in the formation of abnormal fibrosis tissues remains to be established.

Moreover SGK1 and its isoforms are well proved in stimulating the activity and the cell membrane abundance of several transporters and ion channels. For instance, SGK isoforms regulate the epithelial Na+ channel, ENaC (101) , the voltage-gated Na+ channel, SCN5A (101;102), the K+ channels ROMK1 (103), KCNE1/KCNQ1 (104) and Kv1.3 (105), the Na+/H+ exchanger NHE3 (103), the dicarboxylate transporter NaDCT (103), the glutamate transporters EAAT1 (106), EAAT3 (107), EAAT4 (108) and EAAT5 (109) and the Na+/K+- ATPase. The regulatory activity of SGK1 plays a diverse role in essential cell functions such as epithelial transport, excitability, cell proliferation and apoptosis.

[...]

To date, two modes of SGK1 action in regulating transporters and ion channels have been identified. It either regulates transporters by phosphorylating them at the putative consensus site (Arg-Xaa-Arg-Xaa-Xaa-Ser/Thr) or by inhibiting the downregulating effect of protein ubiquitin ligase Nedd4-2. These two modes of regulation of SGK1 were observed in epithelial Na+ channel, ENaC (110) (Figure 5).


85. Lang,F, Klingel,K, Wagner,CA, Stegen,C, Warntges,S, Friedrich,B, Lanzendorfer,M, Melzig,J, Moschen,I, Steuer,S, Waldegger,S, Sauter,M, Paulmichl,M, Gerke,V, Risler,T, Gamba,G, Capasso,G, Kandolf,R, Hebert,SC, Massry,SG, Broer,S: Deranged transcriptional regulation of cell-volume-sensitive kinase hSGK in diabetic nephropathy. Proc.Natl.Acad.Sci.U.S.A 97:8157-8162, 2000

86. Waldegger,S, Klingel,K, Barth,P, Sauter,M, Rfer,ML, Kandolf,R, Lang,F: h-sgk serinethreonine protein kinase gene as transcriptional target of transforming growth factor beta in human intestine. Gastroenterology 116:1081-1088, 1999

87. Kumar,S, Harvey,KF, Kinoshita,M, Copeland,NG, Noda,M, Jenkins,NA: cDNA cloning, expression analysis, and mapping of the mouse Nedd4 gene. Genomics 40:435-443, 1997

90. Waldegger,S, Barth,P, Raber,G, Lang,F: Cloning and characterization of a putative human serine/threonine protein kinase transcriptionally modified during anisotonic and isotonic alterations of cell volume. Proc.Natl.Acad.Sci.U.S.A 94:4440-4445, 1997

96. Klingel,K, Warntges,S, Bock,J, Wagner,CA, Sauter,M, Waldegger,S, Kandolf,R, Lang,F: Expression of cell volume-regulated kinase h-sgk in pancreatic tissue. Am.J.Physiol Gastrointest.Liver Physiol 279:G998-G1002, 2000

101. Chen,SY, Bhargava,A, Mastroberardino,L, Meijer,OC, Wang,J, Buse,P, Firestone,GL, Verrey,F, Pearce,D: Epithelial sodium channel regulated by aldosterone-induced protein sgk. Proc.Natl.Acad.Sci.U.S.A 96:2514-2519, 1999

102. Boehmer,C, Wilhelm,V, Palmada,M, Wallisch,S, Henke,G, Brinkmeier,H, Cohen,P, Pieske,B, Lang,F: Serum and glucocorticoid inducible kinases in the regulation of the cardiac sodium channel SCN5A. Cardiovasc.Res. 57:1079-1084, 2003

103. Yun,CC, Palmada,M, Embark,HM, Fedorenko,O, Feng,Y, Henke,G, Setiawan,I, Boehmer,C, Weinman,EJ, Sandrasagra,S, Korbmacher,C, Cohen,P, Pearce,D, Lang,F: The serum and glucocorticoid-inducible kinase SGK1 and the Na+/H+ exchange regulating factor NHERF2 synergize to stimulate the renal outer medullary K+ channel ROMK1. J.Am.Soc.Nephrol. 13:2823-2830, 2002

104. Embark,HM, Bohmer,C, Vallon,V, Luft,F, Lang,F: Regulation of KCNE1-dependent K(+) current by the serum and glucocorticoid-inducible kinase (SGK) isoforms. Pflugers Arch. 445:601-606, 2003

105. Gamper,N, Fillon,S, Huber,SM, Feng,Y, Kobayashi,T, Cohen,P, Lang,F: IGF-1 upregulates K+ channels via PI3-kinase, PDK1 and SGK1. Pflugers Arch. 443:625-634, 2002

106. Boehmer,C, Henke,G, Schniepp,R, Palmada,M, Rothstein,JD, Broer,S, Lang,F: Regulation of the glutamate transporter EAAT1 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid-inducible kinase isoforms SGK1/3 and protein kinase B. J.Neurochem. 86:1181-1188, 2003

107. Schniepp,R, Kohler,K, Ladewig,T, Guenther,E, Henke,G, Palmada,M, Boehmer,C, Rothstein,JD, Broer,S, Lang,F: Retinal colocalization and in vitro interaction of the glutamate transporter EAAT3 and the serum- and glucocorticoid-inducible kinase SGK1 [correction]. Invest Ophthalmol.Vis.Sci. 45:1442-1449, 2004

108. Rajamanickam,J, Palmada,M, Lang,F, Boehmer,C: EAAT4 phosphorylation at the SGK1 consensus site is required for transport modulation by the kinase. J.Neurochem. 102:858-866, 2007

109. Boehmer,C, Rajamanickam,J, Schniepp,R, Kohler,K, Wulff,P, Kuhl,D, Palmada,M, Lang,F: Regulation of the excitatory amino acid transporter EAAT5 by the serum and glucocorticoid dependent kinases SGK1 and SGK3. Biochem.Biophys.Res.Commun. 329:738-742, 2005

110. Debonneville,C, Flores,SY, Kamynina,E, Plant,PJ, Tauxe,C, Thomas,MA, Munster,C, Chraibi,A, Pratt,JH, Horisberger,JD, Pearce,D, Loffing,J, Staub,O: Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression. EMBO J. 20:7052-7059, 2001

SGK1 was found to stimulate Na+, K+ and 2Cl- cotransporter activity in the thick ascending limb of the kidney, a key nephron segment in urinary concentration, which is of importance in renal Na+ reabsorption9. Abundant SGK1 gene transcription has been observed in diabetic nephropathy10,11,29, fibrosing pancreatitis13 and inflammatory bowel disease19 but SGK1 involvement in the formation of abnormal fibrosis tissues remains to be established.

Moreover SGK1 and its isoforms are well proved in stimulating the activity and the cell membrane abundance of several transporters and ion channels. For instance, SGK isoforms regulate the epithelial Na+ channel, ENaC5, the voltage-gated Na+ channel, SCN5A30, the K+ channels ROMK131, KCNE1/KCNQ132 and Kv1.333-35, the Na+/H+ exchanger NHE336, the dicarboxylate transporter NaDCT37, the glutamate transporters EAAT138, EAAT339, EAAT440 and EAAT541 and the Na+/K+-ATPase42. The regulatory activity of SGK1 plays a diverse role in essential cell functions such as epithelial transport, excitability, cell proliferation and apoptosis.

[page 12]

To date, two modes of SGK1 action in regulating transporters and ion channels have been identified. It either regulates transporters by phosphorylating them at the putative consensus site (Arg-Xaa-Arg-Xaa-Xaa-Ser/Thr) or by inhibiting the downregulating effect of protein ubiquitin ligase Nedd4-2. These two modes of regulation of SGK1 were observed in epithelial Na+ channel, ENaC60,61 (Figure 1).


9. Lang,F. et al. Deranged transcriptional regulation of cell-volume-sensitive kinase hSGK in diabetic nephropathy. Proc. Natl. Acad. Sci. U. S. A 97, 8157-8162 (2000).

10. Waldegger,S. et al. h-sgk serine-threonine protein kinase gene as transcriptional target of transforming growth factor beta in human intestine. Gastroenterology 116, 1081-1088 (1999).

11. Kumar,J.M., Brooks,D.P., Olson,B.A. & Laping,N.J. Sgk, a putative serine/threonine kinase, is differentially expressed in the kidney of diabetic mice and humans. J. Am. Soc. Nephrol. 10, 2488-2494 (1999).

13. Waldegger,S., Barth,P., Raber,G. & Lang,F. Cloning and characterization of a putative human serine/threonine protein kinase transcriptionally modified during anisotonic and isotonic alterations of cell volume. Proc. Natl. Acad. Sci. U. S. A 94, 4440-4445 (1997).

19. Klingel,K. et al. Expression of cell volume-regulated kinase h-sgk in pancreatic tissue. Am. J. Physiol Gastrointest. Liver Physiol 279, G998-G1002 (2000).

29. Hoffman,B.B., Sharma,K., Zhu,Y. & Ziyadeh,F.N. Transcriptional activation of transforming growth factor-beta1 in mesangial cell culture by high glucose concentration. Kidney Int. 54, 1107-1116 (1998).

30. Boehmer,C. et al. Serum and glucocorticoid inducible kinases in the regulation of the cardiac sodium channel SCN5A. Cardiovasc. Res. 57, 1079-1084 (2003).

31. Yun,C.C. et al. The serum and glucocorticoid-inducible kinase SGK1 and the Na+/H+ exchange regulating factor NHERF2 synergize to stimulate the renal outer medullary K+ channel ROMK1. J. Am. Soc. Nephrol. 13, 2823-2830 (2002).

32. Embark,H.M., Bohmer,C., Vallon,V., Luft,F. & Lang,F. Regulation of KCNE1- dependent K(+) current by the serum and glucocorticoid-inducible kinase (SGK) isoforms. Pflugers Arch. 445, 601-606 (2003).

33. Gamper,N. et al. IGF-1 up-regulates K+ channels via PI3-kinase, PDK1 and SGK1. Pflugers Arch. 443, 625-634 (2002).

34. Gamper,N. et al. K+ channel activation by all three isoforms of serum- and glucocorticoid-dependent protein kinase SGK. Pflugers Arch. 445, 60-66 (2002).

35. Warntges,S. et al. Cerebral localization and regulation of the cell volumesensitive serum- and glucocorticoid-dependent kinase SGK1. Pflugers Arch. 443, 617-624 (2002).

36. Yun,C.C., Chen,Y. & Lang,F. Glucocorticoid activation of Na(+)/H(+) exchanger isoform 3 revisited. The roles of SGK1 and NHERF2. J. Biol. Chem. 277, 7676-7683 (2002).

37. Boehmer,C. et al. Stimulation of renal Na+ dicarboxylate cotransporter 1 by Na+/H+ exchanger regulating factor 2, serum and glucocorticoid inducible kinase isoforms, and protein kinase B. Biochem. Biophys. Res. Commun. 313, 998-1003 (2004).

38. Boehmer,C. et al. Regulation of the glutamate transporter EAAT1 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid-inducible kinase isoforms SGK1/3 and protein kinase B. J. Neurochem. 86, 1181-1188 (2003).

39. Schniepp,R. et al. Retinal colocalization and in vitro interaction of the glutamate transporter EAAT3 and the serum- and glucocorticoid-inducible kinase SGK1 [correction]. Invest Ophthalmol. Vis. Sci. 45, 1442-1449 (2004).

40. Bohmer,C. et al. Stimulation of the EAAT4 glutamate transporter by SGK protein kinase isoforms and PKB. Biochem. Biophys. Res. Commun. 324, 1242-1248 (2004).

41. Boehmer,C. et al. Regulation of the excitatory amino acid transporter EAAT5 by the serum and glucocorticoid dependent kinases SGK1 and SGK3. Biochem. Biophys. Res. Commun. 329, 738-742 (2005).

60. Debonneville,C. et al. Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression. EMBO J. 20, 7052-7059 (2001).

61. Friedrich,B. et al. The serine/threonine kinases SGK2 and SGK3 are potent stimulators of the epithelial Na+ channel alpha,beta,gamma-ENaC. Pflugers Arch. 445, 693-696 (2003).

Anmerkungen

The source is not mentioned.

By just copying the original text, Sj has eliminated the correct notation of ionic charges by superscripts

Sichter
(Hindemith), LieschenMueller, (Graf Isolan)

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